The major objective of this research proposal is to attempt to produce modification of atherosclerosis by in vivo modification or blockage of the free E amino groups of lysine in LDL and other liopproteins by dietary means. Previous studies by the applicant, Weigensberg, McMillan and Stary (l) have shown that reducing lysine in the diet can reduce cholesterol atherosclerosis in rabbits and inhibits wound healing (2). The applicant and his group have discovered that l amino 3 imino-propene diacetate can be fed to rabbits, is absorbed into the blood and binds to the free LDL lysine E amino group in vivo and blocks the normal function of these free E amino groups. This will permit us to test the hypothesis that blocking the lysine free E amino group of LDL enhances the removal of LDL and cholesterol out of the blood and into the liver, and lowers LDL and cholesterol concentrations in the blood serum. Until now modification of the free E amino groups of LDL has only been accomplished in vitro by severe chemical reactions, such as by acetocetylation, carbamylation, reductive methylation or by reaction with diketene or tetra methyl acetal of malonyldialdehyde, reactions which would be very difficult it not impossible to achieve in vivo. We propose to test the effects of feeding the amino-imino-propene derivative for its effects on: two types of arterial lesions in rabbits: (i) experimental cholesterol atherosclerosis, (ii) organizing thrombi, (iii) for its ability to lower serum cholesterol and serum LDL levels of hypercholesterol rabbits, (iv) its ability to clear iodine-l25 labelled LDL out of the seruum into the liver, (v) its ability to prevent the accumulation of cholesterol ester in aortic myointimal thickenings produced with balloon catheter in rabbits, (vi) its ability to modify cholesterol ester accumulation in 2 and 4 week old experimental organizing white mural, non-occlusive thrombi in the aortae of rabbits, (vii) its storage in the reticulo-endothelial system, catabolism and excretion in the urine and feces. Lesions will be evaluated in terms of the scientific disciplines of biochemistry and pathology.